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WO2000049407A2 - Procede et dispositif pour representer des particules biologiquement activees faisant varier l'inductance - Google Patents

Procede et dispositif pour representer des particules biologiquement activees faisant varier l'inductance Download PDF

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Publication number
WO2000049407A2
WO2000049407A2 PCT/EP2000/001214 EP0001214W WO0049407A2 WO 2000049407 A2 WO2000049407 A2 WO 2000049407A2 EP 0001214 W EP0001214 W EP 0001214W WO 0049407 A2 WO0049407 A2 WO 0049407A2
Authority
WO
WIPO (PCT)
Prior art keywords
particles
inductivity
changing
measuring
metal coil
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2000/001214
Other languages
German (de)
English (en)
Other versions
WO2000049407A3 (fr
Inventor
Kilian Hennes
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from DE19906352A external-priority patent/DE19906352A1/de
Application filed by Individual filed Critical Individual
Priority to EP00920436A priority Critical patent/EP1198712A2/fr
Priority to CA002370745A priority patent/CA2370745A1/fr
Priority to AU41020/00A priority patent/AU4102000A/en
Publication of WO2000049407A2 publication Critical patent/WO2000049407A2/fr
Anticipated expiration legal-status Critical
Publication of WO2000049407A3 publication Critical patent/WO2000049407A3/fr
Ceased legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/04—Investigating sedimentation of particle suspensions
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/1031—Investigating individual particles by measuring electrical or magnetic effects
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/54326—Magnetic particles
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/06—Investigating concentration of particle suspensions
    • G01N15/0656—Investigating concentration of particle suspensions using electric, e.g. electrostatic methods or magnetic methods
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/01—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials specially adapted for biological cells, e.g. blood cells
    • G01N2015/019—Biological contaminants; Fouling

Definitions

  • the invention relates to a method for the display of biologically activated inductivity-changing — especially ferromagnetic or superparamagnetic
  • the invention also relates to a device for the detection and counting of suspended biological microparticles in liquid samples, in particular for carrying out the method mentioned.
  • Bacteria, blood cells or cell components in aqueous solutions have so far been counted using a flow cytometer or Coulter counter.
  • the corresponding particles are colored and identified using optical signals or paid by capacitive measurements.
  • monovalent primary antibodies are mixed with inductivity-changing, especially ferromagnetic or superparamagnetic, particles in multiple excess, which are coated with secondary antibodies; then, by means of partial sedimentation in a centrifuge, aggregated particles are separated, which consist of a monovalent primary antibody and antibody coated ferromagnetic partial particles exist.
  • inductivity-changing especially ferromagnetic or superparamagnetic, particles in multiple excess, which are coated with secondary antibodies; then, by means of partial sedimentation in a centrifuge, aggregated particles are separated, which consist of a monovalent primary antibody and antibody coated ferromagnetic partial particles exist.
  • viruses or gene probes can also be used, against whose hull proteins or spacer molecules the secondary antibodies are directed.
  • the biological particles for detection or counting can be linked immunologically, phagologically or molecular biologically with aggregated particles which can be measured when subsequently flowing through a metal coil - in particular the gap in a C-shaped metal coil with a ferromagnetic core and trigger affordable changes in inductance.
  • the metal coil as part of an electronic resonant circuit is intended to generate payable changes in the natural oscillation frequency.
  • a different measuring principle is used for the detection of the individual particle: the measurement of the change in inductance of a metal micro coil.
  • biological particles have a permeability constant ⁇ of approximately 1, they have to be marked with inductivity-changing substances beforehand for detection and payment by means of a coil.
  • This labeling takes place through the immunological, phagological or molecular biological coupling of ferromagnetic or superparamagnetic particles which are monovalently linked either to antibodies, to virus docking molecules or to gene probes on spacer molecules.
  • a device of the type mentioned at the outset with a feed line for a sample to be measured, which is surrounded as a measuring line by a metal coil as a measuring coil, which in turn is connected to a device for exciting the vibration and measuring resonance events.
  • this metal coil is placed around an approximately C-shaped core, the ends of which delimit a gap; the measuring line is laid through this gap.
  • the delivery line is connected to a device with capillaries - in particular with Teflon capillaries; the latter are assigned to an electromagnet and can be arranged in a space surrounded by a pole piece.
  • a branch line for excess samples is advantageously provided between the electromagnets and a valve of the delivery line.
  • a resistance and a capacitor can be arranged upstream of that device for exciting the vibration and measuring resonance events towards the metal coil.
  • the measuring coil, a piezo pump arranged upstream of it and a downstream resistor or capacitor are intended to be parts of a microsystem unit.
  • the coupling of the ferromagnetic markers thus takes place in the device, which at the same time enables the particles to be paid to be enriched: the markers are held in that Teflon capillary by means of an electromagnet as a sorption layer until the entire sample has been pumped into the capillary and at the same time the excess sample has run out of the capillary. The magnet is then switched off so that the markers diffuse freely and the surface of the biological particles can sate. Then the capillary content is pumped through the metal coil with the above-mentioned piezoelectric pump, in particular through the gap of the C-shaped metal coil with ferromagnetic core.
  • the metal coil was etched onto a printed circuit board as a spiral and is connected as a resonant circuit with a capacitor and resistor.
  • the oscillating circuit is excited with a frequency that corresponds to the natural oscillation frequency that is generated when an average marked biological microparticle is in the coil or in the gap. This creates a resonance oscillation in the resonant circuit whenever a corresponding microparticle passes through the coil.
  • An example of the application of this method is the detection of coli bacteria in water samples.
  • monovalent primary E. -coli-specific antibodies conjugated to secondary antibodies coupled to megnetic beads The suspension of these conjugates is pumped into the Teflon capillary and fixed there by means of an electromagnet.
  • coli bacteria are retained on the conjugates via the primary antibodies.
  • the suspension of magnetically marked coli bacteria can be pumped through the measuring coil or the gap in the metal coil.
  • the number of resonance events in the connected resonant circuit corresponds to the number of coli bacteria in the original water sample.
  • the detection device uses this measurement method.
  • particles such as bacteria, cells or cell components in aqueous solutions are detected and counted.
  • This technique enables miniaturization of the automatic particle counting process.
  • the particles are marked by reaction with monovalent antibody-coated or virus-coated ferromagnetic particles before the measurement.
  • the inductive measurement is based on passing the ferromagnetic particles aggregated with the biological particles through the microcoil of an electronic resonant circuit designed in the manner described. The resonance events that occur as they pass are counted.
  • the device according to the invention can be used in medicine, microbiology and hygiene, for example for counting blood cells; ecologically relevant microorganisms can be counted or pathogens detected.
  • FIGS. 1, 3 a detail of FIGS. 1, 3 in a schematic oblique view.
  • the reagent with ferromagnetic, biologically activated particles is pumped via lines 12 and 16 into a Teflon capillary 20 and fixed there by means of an electromagnet 22, the magnet coil of which is designated 24 and to which the Z-shaped wound Teflon capillary 20 in a concentric pole shoe 26 is assigned.
  • the free ends 38, 38 a of the measuring coil 36, 36 a are - after a resistor 42 and a capacitor 44 - connected to a device 46 for exciting the vibration and for measuring resonance events; there is a conversion into counts.
  • the number of resonance events in the connected resonant circuit corresponds to the number of coli bacteria in the original water sample Z.
  • a line branch 18 - containing a valve 48 - for excess sample portions Q is provided between the Teflon capillary 20 and the piezo pump 32 .

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Dispersion Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Investigating Or Analyzing Materials By The Use Of Magnetic Means (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne un procédé permettant de représenter des particules biologiquement activées, faisant varier l'inductance, en particulier des particules ferromagnétiques ou superparamagnétiques, selon lequel des anticorps primaires monovalents sont mélangés avec des particules en excès faisant varier l'inductance, qui sont recouvertes avec des anticorps secondaires, et l'on sépare ensuite les particules agrégées par sédimentation partielle. Ces particules sont constituées d'un anticorps primaire monovalent et de particules partielles recouvertes d'anticorps, faisant varier l'inductance. En outre, selon un autre procédé, des virus sont mélangés avec des particules ferromagnétiques en excès qui sont recouvertes d'anticorps dirigés contre les protéines d'enveloppe des virus, et l'on sépare les particules agrégées par sédimentation partielle. Ces particules sont constituées d'un virus et de particules partielles recouvertes d'anticorps, faisant varier l'inductance. Dans un dispositif permettant de détecter et de dénombrer des microparticules biologiques en suspension dans des échantillons liquides, une conduite d'amenée (16) destinée au transport d'un échantillon à mesurer est, en tant que conduite de mesure (14), entourée d'une bobine métallique sous forme de bobine de mesure (36a), et celle-ci est raccordée à un dispositif (46) servant à provoquer la vibration et à mesurer les événements de résonance. La bobine métallique (36a) est placée autour d'un noyau sensiblement en forme de C et elle présente une fente (52) par laquelle passe la conduite de mesure (34).
PCT/EP2000/001214 1999-02-17 2000-02-15 Procede et dispositif pour representer des particules biologiquement activees faisant varier l'inductance Ceased WO2000049407A2 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP00920436A EP1198712A2 (fr) 1999-02-17 2000-02-15 Procede et dispositif pour representer des particules biologiquement activees faisant varier l'inductance
CA002370745A CA2370745A1 (fr) 1999-02-17 2000-02-15 Procede et dispositif pour representer des particules biologiquement activees faisant varier l'inductance
AU41020/00A AU4102000A (en) 1999-02-17 2000-02-15 Method for representing biologically activated inductance-altering particles anddevice for carrying out the method

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE19906352.4 1999-02-17
DE19906352A DE19906352A1 (de) 1999-02-17 1999-02-17 Nachweis- und Zählgerät für suspendierte biologische Partikel
DE19939208.0 1999-08-18
DE19939208A DE19939208C2 (de) 1999-02-17 1999-08-18 Verfahren zum Darstellen von biologisch aktivierten induktivitätsändernden Partikeln zu deren Nachweis und Zählen sowie Vorrichtung dafür

Publications (2)

Publication Number Publication Date
WO2000049407A2 true WO2000049407A2 (fr) 2000-08-24
WO2000049407A3 WO2000049407A3 (fr) 2002-02-07

Family

ID=26051879

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/001214 Ceased WO2000049407A2 (fr) 1999-02-17 2000-02-15 Procede et dispositif pour representer des particules biologiquement activees faisant varier l'inductance

Country Status (4)

Country Link
EP (1) EP1198712A2 (fr)
AU (1) AU4102000A (fr)
CA (1) CA2370745A1 (fr)
WO (1) WO2000049407A2 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004077044A1 (fr) * 2003-02-28 2004-09-10 Forschungszentrum Jülich GmbH Procede et dispositif de detection selective de particules ferromagnetiques ou supraparamagnetiques
WO2007132374A1 (fr) * 2006-05-09 2007-11-22 Koninklijke Philips Electronics N. V. Dispositif de détection magnétique et procédé de détection de particules magnétiques
DE102008057081A1 (de) * 2008-11-13 2010-05-20 Siemens Aktiengesellschaft Vorrichtung und Verfahren zur Bestimmung der Menge ferromagnetischer Partikel in einer Suspension

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0631669B1 (fr) * 1992-03-20 2004-07-14 Abbott Laboratories Tests de liaison fondes sur le magnetisme et mettant en oeuvre des elements de liaison marques magnetiquement
EP0631668B1 (fr) * 1992-03-20 2002-09-04 Abbott Laboratories Determination de l'affinite de liaison mettant en oeuvre des elements de liaison marques magnetiquement
ATE191086T1 (de) * 1994-07-27 2000-04-15 Pilgrimm Herbert Superparamagnetische teilchen, verfahren zur herstellung und deren verwendung
DE19503664C2 (de) * 1995-01-27 1998-04-02 Schering Ag Magnetorelaxometrische Detektion von Analyten
US5736332A (en) * 1995-11-30 1998-04-07 Mandecki; Wlodek Method of determining the sequence of nucleic acids employing solid-phase particles carrying transponders
JP2000502887A (ja) * 1995-11-30 2000-03-14 ウロデック マンデッキ 生体分子の電子的固相アッセイ
DE19615254C2 (de) * 1996-04-18 1999-03-11 Diagnostikforschung Inst Gerät zur höchstempfindlichen magnetischen Detektion von Analyten
US5998224A (en) * 1997-05-16 1999-12-07 Abbott Laboratories Magnetically assisted binding assays utilizing a magnetically responsive reagent
DE19822123C2 (de) * 1997-11-21 2003-02-06 Meinhard Knoll Verfahren und Vorrichtung zum Nachweis von Analyten
US6046585A (en) * 1997-11-21 2000-04-04 Quantum Design, Inc. Method and apparatus for making quantitative measurements of localized accumulations of target particles having magnetic particles bound thereto
DE19906352A1 (de) * 1999-02-17 1999-07-22 Kilian Dr Hennes Nachweis- und Zählgerät für suspendierte biologische Partikel

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004077044A1 (fr) * 2003-02-28 2004-09-10 Forschungszentrum Jülich GmbH Procede et dispositif de detection selective de particules ferromagnetiques ou supraparamagnetiques
US8071027B2 (en) 2003-02-28 2011-12-06 Forschungszentrum Juelich Gmbh Method and device for selectively detecting ferromagnetic or superparamagnetic particles
WO2007132374A1 (fr) * 2006-05-09 2007-11-22 Koninklijke Philips Electronics N. V. Dispositif de détection magnétique et procédé de détection de particules magnétiques
DE102008057081A1 (de) * 2008-11-13 2010-05-20 Siemens Aktiengesellschaft Vorrichtung und Verfahren zur Bestimmung der Menge ferromagnetischer Partikel in einer Suspension

Also Published As

Publication number Publication date
EP1198712A2 (fr) 2002-04-24
WO2000049407A3 (fr) 2002-02-07
AU4102000A (en) 2000-09-04
CA2370745A1 (fr) 2000-08-24

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